Zirconium-89 Production

The PET isotope, Zirconium-89, was successfully produced by the CS-30 cyclotron under the optimized conditions, such as 15.5 MeV energy, 20 µA beam current, 4 h irradiation time, using yttrium-89 metal foil solid target. By this method, approximately 45 mCi of 89Zr bulk was produced. The identity of the Zr-89 was characterized by gamma spectroscopy, TLC, and HPLC analysis.

Chemical separation and purification of irradiated 89Zr were performed on the Triskem ZR-resin cartridge (1 mL), which provided 40 mCi of 89Zr in 89Zr-oxalate form. Further processing through an anion exchange QMA cartridge (Waters) and elution with 1 M HCl converted 89Zr-oxalate to 89ZrCl4 form in high yield (29 mCi).

The 89ZrCl4 was used for radiolabeling various DOTA-coupled and DFO-coupled biomolecules. Radiolabeling of these biomolecules with 89ZrCl4 was performed using a 5.0 M ammonium acetate buffer, and the pH of the reaction mixture was around 7. Under these labeling conditions, high labeling efficiency was achieved. The 89Zr-labeled products were found to be stable for at least 24 h post-labeling. Initial in vitro and in vivo biodistribution is performed. The detailed in vitro and in vivo evaluation with further optimization of the radiolabeling protocol is in progress and will be reported soon. Further optimization of the production method, together with the separation and purification process, is currently in progress and will be reported. Our work plan is:

1. To develop and optimize a method of efficient production of Zr-89 in our Cyclotron facility.

2. Selection of the correct Target material and its preparation.

3. Optimization of post-irradiation separation and purification steps.

4. Characterization and Quality control of Zr-89 by standard techniques (HPLC, TLC, etc.).

5. Preparation of suitable biomolecules for radiolabeling with Zr-89.

6. Optimization of methods for radiolabeling with Zr-89.